EP0305843A2 - Antiviral agent - Google Patents

Antiviral agent Download PDF

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Publication number
EP0305843A2
EP0305843A2 EP88113610A EP88113610A EP0305843A2 EP 0305843 A2 EP0305843 A2 EP 0305843A2 EP 88113610 A EP88113610 A EP 88113610A EP 88113610 A EP88113610 A EP 88113610A EP 0305843 A2 EP0305843 A2 EP 0305843A2
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EP
European Patent Office
Prior art keywords
formula
hydrogen
lyxofuranosyl
anhydro
purine
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EP88113610A
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German (de)
French (fr)
Inventor
Wolfgang Dr. Barth
Dieter Dr. Häbich
Arnold Dr. Paessens
Gert Dr. Streissle
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Bayer AG
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Bayer AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals

Definitions

  • the invention relates to the use of 1- (2,3-anhydro- ⁇ -lyxofuranosyl) purine or 9-pyrimidine nucleosides as antiviral agents in human and veterinary medicine.
  • the epoxides to be used according to the invention are generally defined by the formula (I).
  • This formula preferably says R for a group of the formula and X represents hydrogen or acetyl, propionyl, propylcarbonyl, isopropylcarbonyl or butylcarbonyl.
  • esters can also be used. These generally include pharmaceutically acceptable salts, esters, a salt of such an ester, or else compounds which, when applied, provide the compounds to be used according to the invention as metabolites or degradation products, also called “prodrugs”.
  • Carboxylic acid esters derived from C1-C10 alkyl carboxylic acids, optionally substituted benzoic acids, C1-C6 alkyl sulfonic acids or also mono-, di- or triphosphate esters may be mentioned in particular.
  • Salts which can be mentioned are salts with customary bases, such as, for example, alkali metal salts (for example sodium or potassium salts), alkaline earth metal salts (for example calcium or magnesium salts) or ammonium salts derived from ammonia or organic amines (such as, for example, diethylamine, triethylamine, ethyldiisopropylamine, dibenzylamine, procaine, Dibenzylamine, N-methylmorpholine, dehydroabietylamine, 1-ephenamine or methylpiperidine).
  • alkali metal salts for example sodium or potassium salts
  • alkaline earth metal salts for example calcium or magnesium salts
  • ammonium salts derived from ammonia or organic amines such as, for example, diethylamine, triethylamine, ethyldiisopropylamine, dibenzylamine, procaine, Dibenzylamine, N-methylmorpholine, dehydroa
  • the compounds of the general formula (I) to be used according to the invention have an extraordinarily potent activity against retroviruses. This is demonstrated by the experimental data given below using the example of the Visna virus for 9- (2,3-anhydro- ⁇ -D-lyxofuranosyl) adenine in cell cultures.
  • the Visna virus and the HIV virus are both lentiviruses belonging to the group of retroviruses.
  • fibroblast cells from sheep (5 x 104 cells per well) - suspended in production medium - were fed to each well.
  • This virus dose corresponds to an MOI (multiplicity of infection) of approx. 0.05.
  • the inhibitory concentration was determined microscopically as the concentration at which the cytopathic effect was inhibited by 50%: compared to the untreated virus control, which showed 100% cell destruction.
  • 9- (2,3-anhydro- ⁇ -D-lyxofuranosyl) adenine in a concentration range from 300 ⁇ g / ml to 1 ⁇ g / ml protects the cells infected with Visna virus from virus-induced cell destruction.
  • HIV-induced diseases require selectively acting compounds with a high tolerance. This is especially true for HIV-induced diseases, in which the viruses attack and destroy the cells that are responsible for cellular immunity.
  • Effective compounds against these pathogens should selectively prevent the multiplication of the virus in these cells and prevent reinfection of fresh cells without their function to ward off the virus itself or other pathogens such as e.g. opportunistic infections is affected.
  • the compounds to be used according to the invention are therefore valuable active substances for the treatment or prophylaxis of diseases caused by retroviruses in human and veterinary medicine.
  • the present invention includes pharmaceutical preparations which, in addition to non-toxic, inert pharmaceutically suitable excipients, contain one or more compounds of the formula (I) or which consist of one or more active compounds of the formula (I), and processes for the preparation of these preparations.
  • the present invention also includes pharmaceutical preparations in dosage units.
  • the preparations in the form of individual parts e.g. Tablets, coated tablets, capsules, pills, suppositories and ampoules are available, the active ingredient content of which corresponds to a fraction or a multiple of a single dose.
  • the dosage units can e.g. 1, 2, 3 or 4 single doses or 1/2, 1/3 or 1/4 of a single dose.
  • a single dose preferably contains the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half or a third or a quarter of a daily dose.
  • Non-toxic, inert pharmaceutically suitable carriers are to be understood as solid, semi-solid or liquid diluents, fillers and formulation auxiliaries of all kinds.
  • the tablets, dragees, capsules, pills and granules can be provided with the customary coatings and casings, optionally containing opacifying agents, and can also be composed such that they contain the active ingredient (s) only or preferably in a certain part release of the intestinal tract with a delay, if necessary, whereby polymer substances and waxes can be used as embedding compounds.
  • the active ingredient (s) can optionally also be in microencapsulated form with one or more of the above-mentioned excipients.
  • suppositories can contain the usual water-soluble or water-insoluble excipients, e.g. Polyethylene glycols, fats, e.g. Cocoa fat and higher esters (e.g. C14 alcohol with C16 fatty acid) or mixtures of these substances.
  • water-soluble or water-insoluble excipients e.g. Polyethylene glycols, fats, e.g. Cocoa fat and higher esters (e.g. C14 alcohol with C16 fatty acid) or mixtures of these substances.
  • ointments, pastes, creams and gels can contain the usual carriers, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.
  • carriers e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.
  • Powders and sprays can contain the usual excipients in addition to the active ingredient (s), e.g. Milk sugar, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances.
  • Sprays can also contain the usual propellants, e.g. Chlorofluorocarbons.
  • solutions and emulsions can contain the usual carriers such as solvents, solvents solution mediators and emulsifiers, for example water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, in particular cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glyrofalurine urine, glycerol urine Contain polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances.
  • solvents solvents solution mediators and emulsifiers
  • solutions and emulsions can also be in sterile and blood isotonic form.
  • suspensions can contain the usual carriers such as liquid diluents, e.g. Water, ethyl alcohol, propylene glycol, suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth or mixtures of these substances.
  • liquid diluents e.g. Water, ethyl alcohol, propylene glycol
  • suspending agents e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth or mixtures of these substances.
  • the formulation forms mentioned can also contain colorants, preservatives and additives which improve the smell and taste, e.g. Peppermint oil and eucalyptus oil and sweeteners, e.g. Saccharin.
  • the active compounds of the formula (I) should be present in the pharmaceutical preparations listed above, preferably in a concentration of about 0.1 to 99.5, preferably of about 0.5 to 95% by weight of the total mixture.
  • the pharmaceutical preparations listed above can also contain further active pharmaceutical ingredients.
  • the pharmaceutical preparations listed above are prepared in a conventional manner by known methods, e.g. by mixing the active substance or substances with the carrier substance or substances.
  • the preparations mentioned can be used in humans and animals either orally, rectally, parenterally (intravenously, intramuscularly, subcutaneously), intracisternally, intravaginally, intraperitoneally, locally (powder, ointment, drops) and for the treatment of infections in cavities, body cavities.
  • Injection solutions, solutions and suspensions for oral therapy, gels, infusion formulations, emulsions, ointments or drops are suitable as preparations.
  • ophthalmic and dermatological formulations silver and other salts, ear drops, eye ointments, powder or solutions can be used.
  • suitable formulations can also be ingested through feed or drinking water.
  • gels, powders, powders, tablets, prolonged-release tablets, premixes, concentrates, granules, pellets, tablets, boluses, capsules, aerosols, sprays, inhalants can be used in humans and animals.
  • the compounds according to the invention can be incorporated into other carrier materials such as plastics, (plastic chains for local therapy), collagen or bone cement.
  • the active compound (s) of the formula (I) in total amounts of about 0.5 to about 500, preferably 5 to 100 mg / kg of body weight per 24 hours , if necessary in the form of several single doses, to achieve the desired results.
  • a single dose contains the active ingredient (s) preferably in amounts of about 1 to about 80, in particular 3 to 30 mg / kg body weight.
  • the compounds to be used according to the invention can be given in the usual concentrations and preparations together with the feed or with feed preparations or with the drinking water.

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  • Biochemistry (AREA)
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  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Veterinary Medicine (AREA)
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  • Oncology (AREA)
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Abstract

1-(2,3-Anhydro- beta -lyxofuranosyl)purine or 9-pyrimidine nucleosides of the formula I <IMAGE> in which X and R have the meaning stated in the description, are used in antiviral medicaments for the therapeutic treatment of the human or animal body.

Description

Die Erfindung betrifft die Verwendung von 1-(2,3-Anhy­dro-β-lyxofuranosyl)purin- oder 9-pyrimidinnucleosiden als antivirale Mittel in der Human- und Tiermedizin.The invention relates to the use of 1- (2,3-anhydro-β-lyxofuranosyl) purine or 9-pyrimidine nucleosides as antiviral agents in human and veterinary medicine.

Es ist bekannt, daß 2′,3′-Didesoxynucleoside gegen Retroviren wirksam sind. [H. Mitsuya, S. Broder, Proc. nat. Acad. Sci. USA 38, 1911-1915 (1986); EP-A 206 497].It is known that 2 ', 3'-dideoxynucleosides are effective against retroviruses. [H. Mitsuya, S. Broder, Proc. nat. Acad. Sci. USA 38: 1911-1915 (1986); EP-A 206 497].

Es wurde nun gefunden, daß Epoxide der allgemeinen For­mel (I)

Figure imgb0001
in welcher
R für eine Gruppe der Formel
Figure imgb0002
 wobei
R¹ Wasserstoff oder Acetyl bedeutet,
und
X für Wasserstoff oder
für geradkettiges C₁-C₇-Alkylcarbonyl, Isopropyl­carbonyl, tert. Butylmethylcarbonyl oder Benzoyl steht,
oder ein pharmazeutisch verträgliches Derivat hiervon,
starke antivirale Wirkung gegen Retroviren aufweisen.It has now been found that epoxides of the general formula (I)
Figure imgb0001
 in which
R for a group of the formula
Figure imgb0002
 in which
R¹ is hydrogen or acetyl,
and
X for hydrogen or
for straight-chain C₁-C₇ alkylcarbonyl, isopropylcarbonyl, tert. Butylmethylcarbonyl or benzoyl,
or a pharmaceutically acceptable derivative thereof,
have strong antiviral activity against retroviruses.

Die erfindungsgemäß zu verwendenden Epoxide sind durch die Formel (I) allgemein definiert.The epoxides to be used according to the invention are generally defined by the formula (I).

In dieser Formel steht vorzugsweise
R für eine Gruppe der Formel

Figure imgb0003
und
X für Wasserstoff oder Acetyl, Propionyl, Propyl­carbonyl, Isopropylcarbonyl oder Butylcarbonyl.This formula preferably says
R for a group of the formula
Figure imgb0003
 and
X represents hydrogen or acetyl, propionyl, propylcarbonyl, isopropylcarbonyl or butylcarbonyl.

Besonders bevorzugt sind Verbindungen der allgemeinen Formel (I),
in welcher
R für eine Gruppe der Formel

Figure imgb0004
und
X für wasserstoff steht.Compounds of the general formula (I) are particularly preferred
in which
R for a group of the formula
Figure imgb0004
 and
X stands for hydrogen.

Ganz besonders bevorzugt ist 9-(2,3-Anhydro-β-D-lyxo­furanosyl)adenin.9- (2,3-anhydro-β-D-lyxofuranosyl) adenine is very particularly preferred.

Ebenso verwendbar sind auch pharmazeutisch verträgliche Derivate der Verbindungen der allgemeinen Formel (I). Hierzu gehören im allgemeinen pharmazeutisch verträg­liche Salze, Ester, ein Salz eines solchen Esters, oder aber Verbindungen, die bei Applikation die erfindungs­gemäß zu verwendenden Verbindungen als Stoffwechselpro­dukte oder Abbauprodukte bereitstellen, auch "Prodrugs" genannt. Ester können hierbei Veresterungsprodukte der -OH-Gruppe (X=H) der erfindungsgemäß zu verwendenden Verbindungen der allgemeinen Formel (I) mit Carbonsäu­ren, Sulfonsäuren oder Phosphorsäuren sein. Insbesondere zu nennen seien Carbonsäureester abgeleitet von C₁-C₁₀-­Alkylcarbonsäuren, gegebenenfalls substituierten Benzoe­säuren, C₁-C₆-Alkylsulfonsäuren oder auch Mono-, Di- ­oder Triphosphatester.Pharmaceutically acceptable derivatives of the compounds of the general formula (I) can also be used. These generally include pharmaceutically acceptable salts, esters, a salt of such an ester, or else compounds which, when applied, provide the compounds to be used according to the invention as metabolites or degradation products, also called “prodrugs”. Esters can be esterification products of the —OH group (X = H) of the compounds of the general formula (I) to be used according to the invention with carboxylic acids, sulfonic acids or phosphoric acids. Carboxylic acid esters derived from C₁-C₁₀ alkyl carboxylic acids, optionally substituted benzoic acids, C₁-C₆ alkyl sulfonic acids or also mono-, di- or triphosphate esters may be mentioned in particular.

Als Salze können Salze mit üblichen Basen genannt wer­den, wie beispielsweise Alkalimetallsalze (z.B. Natrium-­oder Kaliumsalze), Erdalkalisalze (z.B. Calcium- oder Magnesiumsalze) oder Ammoniumsalze abgeleitet von Ammo­niak oder organischen Aminen (wie beispielsweise Di­ethylamin, Triethylamin, Ethyldiisopropylamin, Dibenzyl­amin, Prokain, Dibenzylamin, N-Methylmorpholin, Dehydro­abietylamine, 1-Ephenamin oder Methyl-piperidin).Salts which can be mentioned are salts with customary bases, such as, for example, alkali metal salts (for example sodium or potassium salts), alkaline earth metal salts (for example calcium or magnesium salts) or ammonium salts derived from ammonia or organic amines (such as, for example, diethylamine, triethylamine, ethyldiisopropylamine, dibenzylamine, procaine, Dibenzylamine, N-methylmorpholine, dehydroabietylamine, 1-ephenamine or methylpiperidine).

Die erfindungsgemäß zu verwendenden Wirkstoffe sind be­kannt:

  • a) (Uracilderivat): J.F. Codington, R. Fecher, J.J. Fox, J. Org. Chem. 27 (1962), 163, M. Hirata, Chem. Pharm, Bull. 16 (1968), 430.
  • b) Cytosinderivat): D.H. Hollenberg, K.A. Watanabe, J.J. Fox, J. Med. Chem. 20 (1977), 113.
  • c) (Adeninderivat): R. Mengel, M. Bartke, Angew, Chem. 90 (1978), 725 und M.J. Robins, Y. Fouron, R. Mengel, J. Org. Chem. 39 (1974), 1564.
  • d) (Isocytosinderivat): M. Hirata, Chem. Pharm. Bull. 16 (1968), 430
  • e) (Thyminderivat): GB 1049312 und A.V. Papchikhin et. al., Bioorg. Khim, 11 (1985), 1367.
The active ingredients to be used according to the invention are known:
  • a) (uracil derivative): JF Codington, R. Fecher, JJ Fox, J. Org. Chem. 27 (1962), 163, M. Hirata, Chem. Pharm, Bull. 16 (1968), 430.
  • b) cytosine derivative): DH Hollenberg, KA Watanabe, JJ Fox, J. Med. Chem. 20 (1977), 113.
  • c) (adenine derivative): R. Mengel, M. Bartke, Angew, Chem. 90 (1978), 725 and MJ Robins, Y. Fouron, R. Mengel, J. Org. Chem. 39 (1974), 1564.
  • d) (isocytosine derivative): M. Hirata, Chem. Pharm. Bull. 16 (1968), 430
  • e) (thymine derivative): GB 1049312 and AV Papchikhin et. al., Bioorg. Khim, 11 (1985), 1367.

Es wurde im Rahmen von Untersuchungen, die zu der vor­liegenden Erfindung führten, überraschend gefunden, daß die erfindungsgemäß zu verwendenden Verbindungen der allgemeinen Formel (I) eine außerordentlich starke Wir­kung gegen Retroviren besitzen. Dies wird durch die weiter unten angegebenen Versuchsdaten am Beispiel des Visna-Virus für 9-(2,3-Anhydro-β-D-lyxofuranosyl)adenin in Zellkulturen belegt. Das Visna-Virus und das HIV-Vi­rus (Virus der humanen Immundefiziens) gehören beide zu den Lentiviren, die zu der Gruppe der Retroviren gehö­ren.It was surprisingly found in the course of studies which led to the present invention that the compounds of the general formula (I) to be used according to the invention have an extraordinarily potent activity against retroviruses. This is demonstrated by the experimental data given below using the example of the Visna virus for 9- (2,3-anhydro-β-D-lyxofuranosyl) adenine in cell cultures. The Visna virus and the HIV virus (human immunodeficiency virus) are both lentiviruses belonging to the group of retroviruses.

In Zellkulturen, die mit Visna-Virus infiziert sind, treten 5 bis 10 Tage nach der Infektion ausgeprägte virusinduzierte, zytopathische Effekte auf. Durch Behandlung der infizierten Zellkulturen mit 9-(2,3-­Anhydro-β-D-lyxofuranosyl)adenin konnte das Auftreten dieser zytopathischen Effekte verhindert werden. Der Visna-Virus-Test wurde nach der Methode von O. Narayan et al., Journal of Infectious Dieseases 135, 5, 1977, 800-806 durchgeführt. Dazu wurde 9-(2,3-Anhydro-β-D-­lyxofuranosyl)adenin - in Produktionsmedium gelöst - in nicht zytotoxischen Konzentrationen in 96er Microtiter­platten verdünnt. Anschließend wurden Fibroblastenzellen vom Schaf (5 x 10⁴ Zellen pro Napf) - in Produktionsme­dium suspendiert - zu jedem Näpfchen zugeführt. Jedes Näpfchen erhielt dann 50 µl einer Visna-Viruslösung mit einer Titer von ca. 2,5 x 10⁴ TCID₅₀ (TCID = tissue culture infectious dose). Diese Virusdosis entspricht einer MOI (Multiplizität der Infektion) von ca. 0,05.In cell cultures that are infected with Visna virus, pronounced appear 5 to 10 days after the infection virus-induced, cytopathic effects. Treatment of the infected cell cultures with 9- (2,3-anhydro-β-D-lyxofuranosyl) adenine prevented the occurrence of these cytopathic effects. The Visna virus test was carried out according to the method of O. Narayan et al., Journal of Infectious Dieseases 135 , 5, 1977, 800-806. For this purpose, 9- (2,3-anhydro-β-D-lyxofuranosyl) adenine - dissolved in production medium - was diluted in non-cytotoxic concentrations in 96-well microtiter plates. Subsequently, fibroblast cells from sheep (5 x 10⁴ cells per well) - suspended in production medium - were fed to each well. Each well then received 50 ul of a Visna virus solution with a titer of approximately 2.5 x 10⁴ TCID₅₀ (TCID = tissue culture infectious dose). This virus dose corresponds to an MOI (multiplicity of infection) of approx. 0.05.

Unter diesen Infektionsbedingungen resultierte zwischen Tag 5 und Tag 10 in einer Infektionskontrolle ohne Sub­stanz ein virusinduzierter, zytopathischer Effekt. Die infizierten und behandelten Zellen und die Kontrollzel­len wurden 7 Tage bei 37°C, 5 % CO₂ inkubiert.Under these infection conditions, between day 5 and day 10, an infection control without substance resulted in a virus-induced, cytopathic effect. The infected and treated cells and the control cells were incubated for 7 days at 37 ° C, 5% CO₂.

Bei Auftreten des virusinduzierten zytopathogenen Effek­tes in der unbehandelten Viruskontrolle wurden die Kul­turen mit Formalin fixiert und anschließend mit einer Giemsa-Lösung gefärbt. Die inhibitorische Konzentration (IC₅₀ wurde mikroskopisch als die Konzentration ermit­telt, bei der der zytopathische Effekt um 50 % gehemmt wurde: im Vergleich zur unbehandelten Viruskontrolle, die 100 % Zellzerstörung aufwies.When the virus-induced cytopathogenic effect occurred in the untreated virus control, the cultures were fixed with formalin and then stained with a Giemsa solution. The inhibitory concentration (IC₅₀ was determined microscopically as the concentration at which the cytopathic effect was inhibited by 50%: compared to the untreated virus control, which showed 100% cell destruction.

Es wurde gefunden, daß beispielsweise 9-(2,3-Anhydro-β-­D-lyxofuranosyl)adenin in einem Konzentrationsbereich von 300 µg/ml bis zu 1 µg/ml die mit Visna-Virus infi­zierten Zellen vor der virusinduzierten Zellzerstörung schützt.It has been found that, for example, 9- (2,3-anhydro-β-D-lyxofuranosyl) adenine in a concentration range from 300 µg / ml to 1 µg / ml protects the cells infected with Visna virus from virus-induced cell destruction.

Die Therapie von HIV-induzierten Erkrankungen erfordert selektiv wirkende Verbindungen mit einer hohen Verträg­lichkeit. Dies gilt ganz besonders bei HIV-induzierten Erkrankungen, bei denen die Viren die Zellen befallen und zerstören, die für die zelluläre Immunität verant­wortlich sind.The therapy of HIV-induced diseases requires selectively acting compounds with a high tolerance. This is especially true for HIV-induced diseases, in which the viruses attack and destroy the cells that are responsible for cellular immunity.

Wirksame Verbindungen gegen diese Erreger sollten selek­tiv die Vermehrung des Virus in diesen Zellen verhindern und eine Neuinfektion frischer Zellen verhindern, ohne daß ihre Funktion zur Abwehr des Virus selbst oder anderer Krankheitskeime wie z.B. opportunistische Infek­tionen beeinflußt wird.Effective compounds against these pathogens should selectively prevent the multiplication of the virus in these cells and prevent reinfection of fresh cells without their function to ward off the virus itself or other pathogens such as e.g. opportunistic infections is affected.

In weiterführenden Untersuchungen konnte gezeigt werden, daß beispielsweise die Verbindung 9-(2,3-Anhydro-β-D-­lyxofuranosyl)adenin diese Bedingungen erfüllt und die Funktion von T-Zellen nicht beeinflußt.In further investigations it could be shown that, for example, the compound 9- (2,3-anhydro-β-D-lyxofuranosyl) adenine fulfills these conditions and does not affect the function of T cells.

Die erfindungsgemäß zu verwendenden Verbindungen stellen somit wertvolle Wirkstoffe zur Behandlung oder Prophy­laxe von Erkrankungen, hervorgerufen durch Retroviren, in der Human- und Tiermedizin dar.The compounds to be used according to the invention are therefore valuable active substances for the treatment or prophylaxis of diseases caused by retroviruses in human and veterinary medicine.

Als Indikationsgebiete in der Humanmedizin können bei­spielsweise genannt werden:

  • 1. Die Behandlung oder Prophylaxe von menschlichen Retrovirusinfektionen.
  • 2. Für die Behandlung oder Prophylaxe von HIV (Virus der humanen Immundefiziens; früher HTLV III/LAV genannt) verursachten Erkrankungen (AIDS) und den damit assoziierten Stadien wie ARC (AIDS related complex) and LAS (Lymphadenopathie-Syndrom) sowie der durch dieses Virus verursachten Immunschwäche und Encephalopathie.
  • 3. Für die Behandlung oder die Prophylaxe einer HTLV I- oder HTLV II-Infektion.
  • 4. Für die Behandlung oder die Prophylaxe des AIDS-­carrier Zustandes (AIDS-Überträger-Zustand).
Indications for use in human medicine include:
  • 1. The treatment or prophylaxis of human retrovirus infections.
  • 2. For the treatment or prophylaxis of HIV (human immunodeficiency virus; formerly known as HTLV III / LAV) diseases (AIDS) and the associated stages such as ARC (AIDS related complex) and LAS (lymphadenopathy syndrome) as well as those caused by this Virus caused immunodeficiency and encephalopathy.
  • 3. For the treatment or prophylaxis of an HTLV I or HTLV II infection.
  • 4. For the treatment or prophylaxis of the AIDS carrier state (AIDS carrier state).

Als Indikationen in der Tiermedizin können beispielswei­se angeführt werden: Infektionen mit

  • a) Maedi-Visna (bei Schafen und Ziegen)
  • b) progressives Pneumonievirus (PPV) (bei Schafen und Ziegen)
  • c) caprine arthritis encephalitis Virus (bei Schafen und Ziegen)
  • d) Zwoegerziekte Virus (bei Schafen)
  • e) infektiöses Virus der Anämie (des Pferdes)
  • f) Infektionen verursacht durch das Katzenleukämie­virus.
Examples of indications in veterinary medicine are: infections with
  • a) Maedi-Visna (for sheep and goats)
  • b) progressive pneumonia virus (PPV) (in sheep and goats)
  • c) caprine arthritis encephalitis virus (in sheep and goats)
  • d) Zwoegerziezte virus (in sheep)
  • e) infectious anemia (horse) virus
  • f) infections caused by the feline leukemia virus.

Zur vorliegenden Erfindung gehören pharmazeutische Zube­reitungen, die neben nicht-toxischen, inerten pharmazeu­tisch geeigneten Trägerstoffen eine oder mehrere Verbin­dungen der Formel (I) enthalten oder die aus einem oder mehreren Wirkstoffen der Formel (I) bestehen, sowie Ver­fahren zur Herstellung dieser Zubereitungen.The present invention includes pharmaceutical preparations which, in addition to non-toxic, inert pharmaceutically suitable excipients, contain one or more compounds of the formula (I) or which consist of one or more active compounds of the formula (I), and processes for the preparation of these preparations.

Zur vorliegenden Erfindung gehören auch pharmazeutische Zubereitungen in Dosierungseinheiten. Dies bedeutet, daß die Zubereitungen in Form einzelner Teile, z.B. Tabletten, Dragees, Kapseln, Pillen, Suppositorien und Ampullen vorliegen, deren Wirkstoffgehalt einem Bruchteil oder einem Vielfachen einer Einzeldosis entsprechen. Die Dosierungseinheiten können z.B. 1, 2, 3 oder 4 Einzel­dosen oder 1/2, 1/3 oder 1/4 einer Einzeldosis enthal­ten. Eine Einzeldosis enthält vorzugsweise die Menge Wirkstoff, die bei einer Applikation verabreicht wird und die gewöhnlich einer ganzen, einer halben oder einem Drittel oder einem Viertel einer Tagesdosis entspricht.The present invention also includes pharmaceutical preparations in dosage units. This means that the preparations in the form of individual parts, e.g. Tablets, coated tablets, capsules, pills, suppositories and ampoules are available, the active ingredient content of which corresponds to a fraction or a multiple of a single dose. The dosage units can e.g. 1, 2, 3 or 4 single doses or 1/2, 1/3 or 1/4 of a single dose. A single dose preferably contains the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half or a third or a quarter of a daily dose.

Unter nicht-toxischen, inerten pharmazeutisch geeigneten Trägerstoffen sind feste, halbfeste oder flüssige Ver­dünnungsmittel, Füllstoffe und Formulierungshilfsmittel jeder Art zu verstehen.Non-toxic, inert pharmaceutically suitable carriers are to be understood as solid, semi-solid or liquid diluents, fillers and formulation auxiliaries of all kinds.

Als bevorzugte pharmazeutische Zubereitungen seien Ta­bletten, Dragees, Kapseln, Pillen, Granulate, Supposi­torien, Lösungen, Suspensionen und Emulsionen, Pasten, Salben, Gele, Cremes, Lotions, Puder und Sprays genannt. Tabletten, Dragees, Kapseln, Pillen und Granulate können den oder die Wirkstoffe neben den üblichen Trägerstoffen enthalten, wie

  • (a) Füll- und Streckmittel, z.B. Stärken, Milchzucker, Rohrzucker, Glukose, Mannit und Kieselsäure,
  • (b) Bindemittel, z.B. Carboxymethylcellulose, Algina­te, Gelatine, Polyvinylpyrrolidon,
  • (c) Feuchthaltemittel, z.B. Glycerin,
  • (d) Sprengmittel, z.B. Agar-Agar, Calciumcarbonat und Natriumcarbonat,
  • (e) Lösungsverzögerer, z.B. Paraffin und
  • (f) Resorptionsbeschleuniger, z.B. quarternäre Ammo­niumverbindungen,
  • (g) Netzmittel, z.B. Cetylalkohol, Glycerinmonostea­rat,
  • (h) Adsorptionsmittel, z.B. Kaolin und Bentonit und
  • (i) Gleitmittel, z.B. Talkum, Calcium- und Magnesium­stearat und feste Polyethylenglykole oder Gemische der unter (a) bis (i) aufgeführten Stoffe.
Tablets, dragees, capsules, pills, granules, suppositories, solutions, suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays may be mentioned as preferred pharmaceutical preparations. Tablets, coated tablets, capsules, pills and granules can contain the active ingredient (s) in addition to the usual carriers, such as
  • (a) fillers and extenders, for example starches, milk sugar, cane sugar, glucose, mannitol and silica,
  • (b) binders, for example carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone,
  • (c) humectants, for example glycerin,
  • (d) disintegrants, for example agar-agar, calcium carbonate and sodium carbonate,
  • (e) solution retarders, eg paraffin and
  • (f) absorption accelerators, for example quaternary ammonium compounds,
  • (g) wetting agents, for example cetyl alcohol, glycerol monostearate,
  • (h) adsorbents, for example kaolin and bentonite and
  • (i) lubricants, for example talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under (a) to (i).

Die Tabletten, Dragees, Kapseln, Pillen und Granulate können mit den üblichen, gegebenenfalls Opakisierungs­mitteln enthaltenden, Überzügen und Hüllen versehen sein und auch so zusammengesetzt sein, daß sie den oder die Wirkstoffe nur oder bevorzugt in einem bestimmten Teil des Intestinaltraktes gegebenenfalls verzögert abgeben, wobei als Einbettungsmassen z.B. Polymersubstanzen und Wachse verwendet werden können.The tablets, dragees, capsules, pills and granules can be provided with the customary coatings and casings, optionally containing opacifying agents, and can also be composed such that they contain the active ingredient (s) only or preferably in a certain part release of the intestinal tract with a delay, if necessary, whereby polymer substances and waxes can be used as embedding compounds.

Der oder die Wirkstoffe können gegebenenfalls mit einem oder mehreren der oben angegebenen Trägerstoffe auch in mikroverkapselter Form vorliegen.The active ingredient (s) can optionally also be in microencapsulated form with one or more of the above-mentioned excipients.

Suppositorien können neben dem oder den Wirkstoffen die üblichen wasserlöslichen oder wasserunlöslichen Träger­stoffe enthalten, z.B. Polyethylenglykole, Fette, z.B. Kakaofett und höhere Ester (z.B. C₁₄-Alkohol mit C₁₆-­Fettsäure) oder Gemische dieser Stoffe.In addition to the active ingredient (s), suppositories can contain the usual water-soluble or water-insoluble excipients, e.g. Polyethylene glycols, fats, e.g. Cocoa fat and higher esters (e.g. C₁₄ alcohol with C₁₆ fatty acid) or mixtures of these substances.

Salben, Pasten, Cremes und Gele können neben dem oder den Wirkstoffen die üblichen Trägerstoffe enthalten, z.B. tierische und pflanzliche Fette, Wachse, Paraffine, Stärke, Tragant, Cellulosederivate, Polyethylenglykole, Silikone, Bentonite, Kieselsäure, Talkum und Zinkoxid oder Gemische dieser Stoffe.In addition to the active ingredient (s), ointments, pastes, creams and gels can contain the usual carriers, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.

Puder und Sprays können neben dem oder den Wirkstoffen die üblichen Trägerstoffe enthalten, z.B. Milchzucker, Talkum, Kieselsäure, Aluminiumhydroxid, Calciumsilikat und Polyamidpulver oder Gemische dieser Stoffe. Sprays können zusätzlich die üblichen Treibmittel, z.B. Chlor­fluorkohlenwasserstoffe, enthalten.Powders and sprays can contain the usual excipients in addition to the active ingredient (s), e.g. Milk sugar, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays can also contain the usual propellants, e.g. Chlorofluorocarbons.

Lösungen und Emulsionen können neben dem oder den Wirk­stoffen die üblichen Trägerstoffe wie Lösungsmittel, Lö­ sungsvermittler und Emulgatoren, z.B. Wasser, Ethylalko­hol, Isopropylalkohol, Ethylcarbonat, Ethylacetat, Ben­zylalkohol, Benzylbenzoat, Propylenglykol, 1,3-Butylen­glykol, Dimethylformamid, Öle, insbesondere Baumwoll­saatöl, Erdnußöl, Maiskeimöl, Olivenöl, Ricinusöl und Sesamöl, Glycerin, Glycerinformal, Tetrahydrofurfuryl­alkohol, Polyethylenglykole und Fettsäureester des Sorbitans oder Gemische dieser stoffe enthalten.In addition to the active ingredient (s), solutions and emulsions can contain the usual carriers such as solvents, solvents solution mediators and emulsifiers, for example water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, in particular cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glyrofalurine urine, glycerol urine Contain polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances.

Zur parenteralen Applikation können die Lösungen und Emulsionen auch in steriler und blutisotonischer Form vorliegen.For parenteral administration, the solutions and emulsions can also be in sterile and blood isotonic form.

Suspensionen könne neben dem oder den Wirkstoffen die üblichen Trägerstoffe wie flüssige Verdünnungsmittel, z.B. Wasser, Ethylakohol, Propylenglykol, Suspendier­mittel, z.B. ethoxylierte Isostearylalkohole, Polyoxy­ethylensorbit- und Sorbitan-Ester, mikrokristalline Cellulose, Aluminiummetahydroxid, Bentonit, Agar-Agar und Tragant oder Gemische dieser Stoffe enthalten.In addition to the active ingredient (s), suspensions can contain the usual carriers such as liquid diluents, e.g. Water, ethyl alcohol, propylene glycol, suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth or mixtures of these substances.

Die genannten Formulierungsformen können auch Färbe­mittel, Konservierungsstoffe sowie geruchs- und ge­schmacksverbesserte Zusätze, z.B. Pfefferminzöl und Eukalyptusöl und Süßmittel, z.B. Saccharin, enthalten.The formulation forms mentioned can also contain colorants, preservatives and additives which improve the smell and taste, e.g. Peppermint oil and eucalyptus oil and sweeteners, e.g. Saccharin.

Die Wirkstoffe der Formel (I) sollen in den oben aufge­führten pharmazeutischen Zubereitungen, vorzugsweise in einer Konzentration von etwa 0,1 bis 99,5, vorzugsweise von etwa 0,5 bis 95 Gew.-%, der Gesamtmischung vorhanden sein.The active compounds of the formula (I) should be present in the pharmaceutical preparations listed above, preferably in a concentration of about 0.1 to 99.5, preferably of about 0.5 to 95% by weight of the total mixture.

Die oben aufgeführten pharmazeutischen Zubereitungen können außer den Verbindungen der Formel (I) auch weite­re pharmazeutische Wirkstoffe enthalten.In addition to the compounds of the formula (I), the pharmaceutical preparations listed above can also contain further active pharmaceutical ingredients.

Die Herstellung der oben aufgeführten pharmazeutischen Zubereitungen erfolgt in üblicher Weise nach bekannten Methoden, z.B. durch Mischen des oder der Wirkstoffe mit dem oder den Trägerstoffen.The pharmaceutical preparations listed above are prepared in a conventional manner by known methods, e.g. by mixing the active substance or substances with the carrier substance or substances.

Die genannten Zubereitungen können bei Mensch und Tier entweder oral, rektal, parenteral (intravenös, intramus­kulär, subkutan), intracisternal, intravaginal, intrape­ritoneal, lokal (Puder, Salbe, Tropfen) und zur Therapie von Infektionen in Hohlräumen, Körperhöhlen angewendet werden. Als geeignet Zubereitungen kommen Injektionslö­sungen, Lösungen und Suspensionen für die orale Thera­pie, Gele, Aufgußformulierunge, Emulsionen, Salben oder Tropfen in Frage. Zur lokalen Therapie können ophthalmo logische und dermatologische Formulierungen, Silber- und andere Salze, Ohrentropfen, Augensalben, Puder oder Lö­sungen verwendet werden. Bei Tieren kann die Aufnahme auch über das Futter oder Trinkwasser in geeigneten For­mulierungen erfolgen. Ferner können Gele, Pulver, Puder, Tabletten, Retard-Tabletten, Premixe, Konzentrate, Gra­nulate, Pellets, Tabletten, Boli, Kapseln, Aerosole, Sprays, Inhalate bei Mensch und Tier angewendet werden. Ferner können die erfindungsgemäßen Verbindungen in andere Trägermaterialien wie zum Beispiel Kunststoffe, (Kunststoffketten zur lokalen Therapie), Kollagen oder Knochenzement eingearbeitet werden.The preparations mentioned can be used in humans and animals either orally, rectally, parenterally (intravenously, intramuscularly, subcutaneously), intracisternally, intravaginally, intraperitoneally, locally (powder, ointment, drops) and for the treatment of infections in cavities, body cavities. Injection solutions, solutions and suspensions for oral therapy, gels, infusion formulations, emulsions, ointments or drops are suitable as preparations. For local therapy, ophthalmic and dermatological formulations, silver and other salts, ear drops, eye ointments, powder or solutions can be used. In animals, suitable formulations can also be ingested through feed or drinking water. Furthermore, gels, powders, powders, tablets, prolonged-release tablets, premixes, concentrates, granules, pellets, tablets, boluses, capsules, aerosols, sprays, inhalants can be used in humans and animals. Furthermore, the compounds according to the invention can be incorporated into other carrier materials such as plastics, (plastic chains for local therapy), collagen or bone cement.

Im allgemeinen hat es sich sowohl in der Human- als auch in der Veterinärmedizin als vorteilhaft erwiesen, den oder die Wirkstoffe der Formel (I) in Gesamtmengen von etwa 0,5 bis etwa 500, vorzugsweise 5 bis 100 mg/kg Körpergewicht je 24 Stunden, gegebenenfalls in Form mehrerer Einzelgaben, zur Erzielung der gewünschten Ergebnisse zu verabreichen. Eine Einzelgabe enthält den oder die Wirkstoffe vorzugsweise in Mengen von etwa 1 bis etwa 80, insbesondere 3 bis 30 mg/kg Körpergewicht. Es kann jedoch erforderlich sein, von den genannten Do­sierungen abzuweichen, und zwar in Abhängigkeit von der Art und dem Körpergewicht des zu behandelnden Objekts, der Art und der Schwere der Erkrankung, der Art der Zu­bereitung und der Applikation des Arzneimittels sowie dem Zeitraum bzw. Intervall, innerhalb welchem die Ver­abreichung erfolgt.In general, it has proven to be advantageous both in human and in veterinary medicine to use the active compound (s) of the formula (I) in total amounts of about 0.5 to about 500, preferably 5 to 100 mg / kg of body weight per 24 hours , if necessary in the form of several single doses, to achieve the desired results. A single dose contains the active ingredient (s) preferably in amounts of about 1 to about 80, in particular 3 to 30 mg / kg body weight. However, it may be necessary to deviate from the doses mentioned, depending on the type and body weight of the object to be treated, the type and severity of the disease, the type of preparation and administration of the drug, and the period or interval within which the administration takes place.

So kann es in einigen Fällen ausreichend sein, mit weni­ger als der obengenannten Menge Wirkstoff auszukommen, während in anderen Fällen die oben angeführte Wirkstoff­menge überschritten werden muß. Die Festlegung der je­weils erforderlichen optimalen Dosierung und Applika­tionsart der Wirkstoffe kann durch jeden Fachmann auf­grund seines Fachwissens leicht erfolgen.In some cases it may be sufficient to make do with less than the above-mentioned amount of active ingredient, while in other cases the above-mentioned amount of active ingredient must be exceeded. The optimum dosage and type of application of the active ingredients required in each case can easily be determined by any person skilled in the art on the basis of his specialist knowledge.

Die erfindungsgemäß zu verwendenden Verbindungen können in den üblichen Konzentrationen und Zubereitungen zusam­men mit dem Futter bzw. mit Futterzubereitungen oder mit dem Trinkwasser gegeben werden.The compounds to be used according to the invention can be given in the usual concentrations and preparations together with the feed or with feed preparations or with the drinking water.

Claims (16)

1. Arzneimittel enthaltend mindestens ein 1-(2,3-­Anhydro-β-D-lyxofuranosyl)purin- oder 9-pyrimidin­nucleosid der Formel I
Figure imgb0005
 in welcher
R für eine Gruppe der Formel
Figure imgb0006
 wobei
R¹ Wasserstoff oder Acetyl bedeutet,
und
X für Wasserstoff oder
für geradkettiges C₁-C₇-Alkylcarbonyl, Isopro­pylcarbonyl, tert. Butylmethylcarbonyl oder Benzoyl steht,
oder ein pharmazeutisch verträgliches Derivat hier­von.1. Medicament containing at least one 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleoside of the formula I.
Figure imgb0005
 in which
R for a group of the formula
Figure imgb0006
 in which
R¹ is hydrogen or acetyl,
and
X for hydrogen or
for straight-chain C₁-C₇ alkylcarbonyl, isopropylcarbonyl, tert. Butylmethylcarbonyl or benzoyl,
or a pharmaceutically acceptable derivative thereof. 2. Arzneimittel enthaltend mindestens ein 1-(2,3-­Anhydro-β-D-lyxofuranosyl)purin- oder 9-pyrimidin­nucleosid der Formel (I) in Anspruch 1
in welcher
R für eine Gruppe der Formel
Figure imgb0007
 X für Wasserstoff oder Acetyl, Propionyl, Pro­pylcarbonyl, Isopropylcarbonyl oder Butyl­carbonyl steht.2. Medicament containing at least one 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleoside of the formula (I) in claim 1
in which
R for a group of the formula
Figure imgb0007
 X represents hydrogen or acetyl, propionyl, propylcarbonyl, isopropylcarbonyl or butylcarbonyl. 3. Arzneimittel enthaltend mindestens ein 1-(2,3-Anhy­dro-β-D-lyxofuranosyl)purin- oder 9-pyrimidin­nucleosid der Formel (I) nach Anspruch 1
in welcher
R für eine Gruppe der Formel
Figure imgb0008
 und
X für Wasserstoff steht.3. Medicament containing at least one 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleoside of the formula (I) according to claim 1
in which
R for a group of the formula
Figure imgb0008
 and
X stands for hydrogen. 4. Arzneimittel enthaltend 1-(2,3-Anhydro-β-D-lyxo­furanosyl)purin- oder 9-pyrimidinnucleoside.4. Medicament containing 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleosides. 5. Epoxide der allgemeinen Formel (I)
Figure imgb0009
 in welcher
R für eine Gruppe der Formel
Figure imgb0010
 wobei
R¹ Wasserstoff oder Acetyl bedeutet,
und
X für Wasserstoff oder
für geradkettiges C₁-C₇-Alkylcarbonyl, Iso­propylcarbonyl, tert. Butylmethylcarbonyl oder Benzoyl steht,
oder ein pharmazeutisch verträgliches Derivat hier­von,
zur Anwendung in einem Verfahren zur therapeuti­schen Behandlung des menschlichen oder tierischen Körpers.5. Epoxides of the general formula (I)
Figure imgb0009
 in which
R for a group of the formula
Figure imgb0010
 in which
R¹ is hydrogen or acetyl,
and
X for hydrogen or
for straight-chain C₁-C₇ alkylcarbonyl, isopropylcarbonyl, tert. Butylmethylcarbonyl or benzoyl,
or a pharmaceutically acceptable derivative thereof,
for use in a method for the therapeutic treatment of the human or animal body. 6. 1-(2,3-Anhydro-β-D-lyxofuranosyl)purin- oder 9-py­rimidinnucleoside zur Anwendung in einem Verfahren zur therapeutischen Behandlung des menschlichen oder tierischen Körpers.6. 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleosides for use in a method for the therapeutic treatment of the human or animal body. 7. 1-(2,3-Anhydro-β-D-lyxofuranosyl)purin- oder 9-py­rimidinnucleoside der formel (I)
Figure imgb0011
 in welcher
R für eine Gruppe der Formel
Figure imgb0012
 wobei
R¹ Wasserstoff oder Acetyl bedeutet
und
X für Wasserstoff,
für geradkettiges C₁-C₇-Alkylcarbonyl, Isopro­pylcarbonyl, tert, Butylmethylcarbonyl oder Benzoyl steht,
oder ein pharmazeutisch verträgliches Derivat hier­von.7. 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleosides of the formula (I)
Figure imgb0011
 in which
R for a group of the formula
Figure imgb0012
 in which
R1 is hydrogen or acetyl
and
X for hydrogen,
represents straight-chain C₁-C₇ alkylcarbonyl, isopropylcarbonyl, tert, butylmethylcarbonyl or benzoyl,
or a pharmaceutically acceptable derivative thereof. 8. 1-(2,3-Anhydro-β-D-lyxofuranosyl)purin- oder 9-py­rimidinnucleoside zur Behandlung von viralen Infek­tionen.8. 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleosides for the treatment of viral infections. 9. Epoxide der Formel (I)
Figure imgb0013
 in welcher
R für eine Gruppe der Formel
Figure imgb0014
 R¹ Wasserstoff oder Acetyl bedeutet,
und
X für Wasserstoff oder
für geradkettiges C₁-C₇-Alkylcarbonyl, Isopro­pylcarbonyl, tert. Butylmethylcarbonyl oder Benzoyl steht,
oder ein pharmazeutisch verträgliches Derivat hier­von,
zur Behandlung von retroviralen Infektionen.9. Epoxides of the formula (I)
Figure imgb0013
 in which
R for a group of the formula
Figure imgb0014
 R¹ is hydrogen or acetyl,
and
X for hydrogen or
for straight-chain C₁-C₇ alkylcarbonyl, isopropylcarbonyl, tert. Butylmethylcarbonyl or benzoyl,
or a pharmaceutically acceptable derivative thereof,
for the treatment of retroviral infections. 10. 1-(2,3-Anhydro-β-D-lyxofuranosyl)purin- oder 9-py­rimidinnucleoside zur Behandlung von retroviralen Infektionen.10. 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleosides for the treatment of retroviral infections. 11. Epoxide der Formel (I)
Figure imgb0015
 in welcher
R für eine Gruppe der Formel
Figure imgb0016
Figure imgb0017
 wobei
R¹ Wasserstoff oder Acetyl bedeutet,
und
X für Wasserstoff oder
für geradkettiges C₁-C₇-Alkylcarbonyl, Isopro­pylcarbonyl, tert. Butylmethylcarbonyl oder Benzoyl steht,
oder ein pharmazeutisch verträgliches Derivat hier­von,
zur Prophylaxe von viralen Infektionen.11. Epoxides of the formula (I)
Figure imgb0015
 in which
R for a group of the formula
Figure imgb0016
Figure imgb0017
 in which
R¹ is hydrogen or acetyl,
and
X for hydrogen or
for straight-chain C₁-C₇ alkylcarbonyl, isopropylcarbonyl, tert. Butylmethylcarbonyl or benzoyl,
or a pharmaceutically acceptable derivative thereof,
for the prophylaxis of viral infections. 12. 1-(2,3-Anhydro-β-D-lyxofuranosyl)purin- oder 9-py­rimidinnucleoside zur Prophylaxe von viralen Infek­tionen.12. 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleosides for the prophylaxis of viral infections. 13. Epoxide der Formel (I)
Figure imgb0018
 in welcher
R für eine Gruppe der formel
Figure imgb0019
 wobei
R¹ Wasserstoff oder Acetyl bedeutet,
und
X für Wasserstoff oder
für geradkettiges C₁-C₇-Alkylcarbonyl, Isopro­pylcarbonyl, tert. Butylmethylcarbonyl oder Benzoyl steht,
oder ein pharmazeutisch verträgliches Derivat hier­von,
zur Prophylaxe von retroviralen Infektionen.13. Epoxides of the formula (I)
Figure imgb0018
 in which
R for a group of the formula
Figure imgb0019
 in which
R¹ is hydrogen or acetyl,
and
X for hydrogen or
for straight-chain C₁-C₇ alkylcarbonyl, isopropylcarbonyl, tert. Butylmethylcarbonyl or benzoyl,
or a pharmaceutically acceptable derivative thereof,
for the prophylaxis of retroviral infections. 14. 1-(2,3-Anhydro-β-D-lyxofuranosyl)purin- oder 9-py­rimidinnucleoside zur Prophylaxe von retroviralen Infektionen.14. 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleosides for the prophylaxis of retroviral infections. 15. Verwendung von Epoxiden der Formel (I)
Figure imgb0020
 in welcher
R für eine Gruppe der formel
Figure imgb0021
 wobei
R¹ Wasserstoff oder Acetyl bedeutet,
und
X für Wasserstoff oder
für geradkettiges C₁-C₇-Alkylcarbonyl, Isopro­pylcarbonyl, tert. Butylmethylcarbonyl oder Benzoyl steht,
oder ein pharmazeutisch verträgliches Derivat hier­von,
zur Herstellung von antiviralen Mitteln.15. Use of epoxides of the formula (I)
Figure imgb0020
 in which
R for a group of the formula
Figure imgb0021
 in which
R¹ is hydrogen or acetyl,
and
X for hydrogen or
for straight-chain C₁-C₇ alkylcarbonyl, isopropylcarbonyl, tert. Butylmethylcarbonyl or benzoyl,
or a pharmaceutically acceptable derivative thereof,
for the production of antiviral agents. 16. Verwendung von 1-(2,3-Anhydro-β-D-lyxofurano­syl)purin- oder 9-pyrimidinnucleosiden zur Her­stellung von antiviralen Mitteln.16. Use of 1- (2,3-anhydro-β-D-lyxofuranosyl) purine or 9-pyrimidine nucleosides for the preparation of antiviral agents.
EP88113610A 1987-09-01 1988-08-22 Antiviral agent Withdrawn EP0305843A2 (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5556639A (en) * 1991-01-30 1996-09-17 Glaxo Wellcome Inc. Water-dispersible tablets
US5629016A (en) * 1991-01-30 1997-05-13 Glaxo Wellcome Inc. Water-dispersible tablets
US5698221A (en) * 1992-07-27 1997-12-16 Patel; Suryakant Dahyabhai Water-dispersible tablets
US5698226A (en) * 1993-07-13 1997-12-16 Glaxo Wellcome Inc. Water-dispersible tablets

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4978655A (en) * 1986-12-17 1990-12-18 Yale University Use of 3'-deoxythymidin-2'-ene (3'deoxy-2',3'-didehydrothymidine) in treating patients infected with retroviruses

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5556639A (en) * 1991-01-30 1996-09-17 Glaxo Wellcome Inc. Water-dispersible tablets
US5629016A (en) * 1991-01-30 1997-05-13 Glaxo Wellcome Inc. Water-dispersible tablets
US5660860A (en) * 1991-01-30 1997-08-26 Glaxo Wellcome Inc. Water-dispersible tablets
US5698221A (en) * 1992-07-27 1997-12-16 Patel; Suryakant Dahyabhai Water-dispersible tablets
US5698226A (en) * 1993-07-13 1997-12-16 Glaxo Wellcome Inc. Water-dispersible tablets

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AU2169188A (en) 1989-03-02
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DK485088D0 (en) 1988-08-31
DK485088A (en) 1989-03-02
KR890005140A (en) 1989-05-13

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